Increased trinucleotide repeat instability with advanced maternal age

Michael D. Kaytor, Eric N. Burright, Lisa A. Duvick, Huda Y. Zoghbi, Harry T. Orr

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Nucleotide repeat instability is associated with an increasing number of cancers and neurological disorders. The mechanisms that govern repeat instability in these biological disorders are not well understood. To examine genetic aspects of repeat instability we have introduced an expanded CAG trinucleotide repeat into transgenic mice. We have detected intergenerational CAG repeat instability in transgenic mice only when the transgene was maternally transmitted. These intergenerational instabilities increased in frequency and magnitude as the transgenic mother aged. Furthermore, triplet repeat variations were detected in unfertilized oocytes and were comparable with those in the offspring. These data show that maternal repeat instability in the transgenic mice occurs after meiotic DNA replication and prior to oocyte fertilization. Thus, these findings demonstrate that advanced maternal age is an important factor for instability of nucleotide repeats in mammalian DNA.

Original languageEnglish (US)
Pages (from-to)2135-2139
Number of pages5
JournalHuman molecular genetics
Volume6
Issue number12
DOIs
StatePublished - Nov 1 1997

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